Xiaofei An

Rationale: Immune checkpoint inhibitors, particularly programmed cell death protein 1 (PD-1) blockers, have transformed cancer therapy but can induce immune-related endocrine toxicities. Severe involvement of multiple endocrine axes, including dual pituitary dysfunction, is rare and challenging to diagnose due to nonspecific clinical features. Highlighting such cases can improve early recognition and management. Patient concerns: A 56-year-old man with esophageal cancer developed fatigue, polyuria, polydipsia, dizziness, and severe hyponatremia after treatment with tislelizumab, a PD-1 inhibitor. Diagnoses: Laboratory evaluation revealed new-onset autoimmune diabetes, hypothyroidism, and secondary adrenal insufficiency. The constellation of biochemical abnormalities and clinical features, in the absence of alternative etiologies, indicated immune-related hypophysitis and pancreatic islet injury. Two additional cases of severe, recurrent hyponatremia after PD-1 therapy were also reviewed. Interventions: The patient received targeted hormone replacement therapy, including glucocorticoids and levothyroxine, along with insulin for glycemic control. Outcomes: Symptoms improved significantly, and biochemical parameters normalized following treatment, demonstrating effective management of multi-glandular endocrine failure induced by PD-1 blockade. Lessons: PD-1 inhibitors can cause severe, concurrent dysfunction of multiple endocrine organs. Clinicians should maintain high vigilance, implement proactive screening for pituitary and metabolic abnormalities during and after immune checkpoint inhibitor therapy, and adopt a multidisciplinary approach to ensure timely diagnosis and treatment.